Apparatus and Method for Cardiac Tissue Modulation by Topical Application of Vacuum to Minimize Cell Death and Damage

ABSTRACT

A method and apparatus are provided for treating cardiac tissue to modulate ischemic heart tissue with topical sub-atmospheric pressure to minimize cell death and damage.

RELATED APPLICATIONS

The present application claims the benefit of priority of U.S.Provisional Application 61/088,558, filed on Aug. 13, 2008 and U.S.Provisional Application No. 61/081,997, filed on Jul. 18, 2008, theentire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to a method and apparatus fortreating cardiac tissue, and more particularly, but not exclusively, tomodulating ischemic and reperfused heart tissue with topicalsub-atmospheric pressure to minimize cell death and damage.

BACKGROUND OF THE INVENTION

Myocardial ischemia occurs when a portion of the heart does not receivesufficient oxygen and energy substrates to meet its demand. This usuallyoccurs because of a blockage in the artery due to either atheroscleroticplaque or thrombus formation. In a myocardial infarction there is anarea of injury where the cells, because of lack of blood flow, will dieimmediately. There is a layer adjacent where there is impaired bloodflow that is equivalent to the zone of stasis and there is a moreperipheral unaffected zone. Unfortunately the infarcted heart willattempt to increase rate of contracture and overall work to compensatefor areas of the heart that are not functioning adequately.Consequentially the areas that are in the “zone of stasis” are calledupon to do more work which will increase the energy requirements placedupon them and will subsequently result in further progression of death.If left untreated, this ischemia will lead to an expanding zone ofinfarction that may eventually extend transmurally across the thicknessof the ventricle.

Limiting the degree of infarction resulting from myocardial ischemia isparamount to improving both short- and long-term outcomes in patients.Therefore, in order to salvage this myocardial tissue, timelyreperfusion (re-establishment of coronary blood flow) of the tissue musttake place. The amount of salvageable tissue within an ischemic zone isdependent on the timeliness of reperfusion. While reperfusion halts theischemic processes by delivering oxygen and nutrients (including energysubstrates), this process also rapidly sets into motion a series ofevents and cascades that exacerbates injury, extending the area ofnecrosis beyond that encountered during ischemia alone. Much of thisreperfusion injury appears to be inflammatory in nature, butinappropriately directed against host tissues instead of foreignsubstances. Being able to reduce this reperfusion injury allows for thesalvage of the greatest amount of myocardium.

Reperfusion injury manifests itself in a number of ways, includingmyocardial dysfunction (myocardial stunning), arrhythmias, and acollection of events that result in lethal reperfusion injury.Currently, there are effective pharmacologic therapies to treatreperfusion arrhythmias, and myocardial stunning will generally resolveby itself given time, leaving the mediators of lethal reperfusion injuryas the logical targets in an attempt to preserve ischemic-reperfused,but viable tissue.

There are a large number of potential mediators of lethal reperfusioninjury including calcium overload, oxygen radicals, changes in osmoticgradients (and subsequent cell swelling), the mitochondrial permeabilitytransition pore, and inflammation (itself a complex set of cascades andmediators including complement activation, leukocyte infiltration andpro-inflammatory cytokines and mediators). In addition, thecardioprotective effects of selective inhibition of any and all of thesephenomenon, including antioxidants, sodium-hydrogen exchange inhibitors,anti-inflammatory agents (including adenosine, adhesion moleculeantibodies and complement inhibitors) in animal models of myocardialischemia-reperfusion are known. However, very few have demonstrated anydegree of clinical success in people, likely due to the fact that thesetherapeutics act selectively at a single point within a cascade ofevents, or on a single facet of a very complex and multifaceted process.Thus, though the application of negative (or sub-atmospheric) pressuretherapy to wounded cutaneous and subcutaneous tissue demonstrates anincreased rate of healing compared to traditional methods (as set forthin U.S. Pat. Nos. 5,645,081, 5,636,643, 7,198,046, and 7,216,651, aswell as US Published Application Nos. 2003/0225347, 2004/0039391, and2004/0122434, the contents of which are incorporated herein byreference), there remains a need in the art for devices and methods fortreating myocardial ischemia. In these type wounds of cutaneous andsubcutaneous wounds the screen/dressing can often be easily andnon-invasively changed at routine, pre-determined intervals withoutsignificant disruption to the healing tissues. However, when techniquesare used to treat tissues or organs in which the overlying skin isintact, the overlying skin must be surgically disrupted by thedeliberate creation of a wound through the overlying tissue to exposethe tissue or organ that was originally injured. The overlying,originally healthy tissues which were disrupted to expose the injuredtissue can be sutured closed over top of the injured tissue. This allowsfor negative pressure treatment of the wounded tissues with restorationof the suprawound tissues. Current commercially available embodiments ofnegative pressure dressings and cover are not biodegradable orbioresorbable. This lack of biodegradability/bioresorbabilitynecessitates re-opening of the sutured incision, removal of the dressingand cover, placement of a new dressing and cover, and again suturing theincision closed. This sequence would have to be repeated until theoriginal wounded tissue is healed, with one final re-opening of theincision to remove the dressing and cover. Every time the incision isopened to change or remove the dressing and cover, it increases the riskthat the site will become infected.

SUMMARY OF THE INVENTION

The present invention relates to devices and methods for treatingdamaged heart tissue, such as myocardial infarction in the ischemic orearly reperfusion phase, by treatment with sub-atmospheric (or negative)pressure. Treatment with the devices and methods of the presentinvention may salvage cells in the zone of stasis and thereby decreasethe size of the infarct. Such treatment would be especially efficaciousin endstage myocardial disease where bypass or stenting would not bepossible. The treatment would also be useful as an adjunct to ECMO(extracorporeal membrane oxygenation) for resting the heart, followingcardiac arrest, in situations with left main artery lesions, etc.

An exemplary negative pressure therapy device of the present inventionmay include a vacuum dressing, e.g., porous material, for placement overthe tissue to be treated. The vacuum dressing may be bio-incorporable innature so that a second stage for removal would not be required. (Asused herein the term “bio-incorporable” is defined to describe amaterial that may be left in the patient indefinitely and is capable ofbeing remodeled, resorbed, dissolved, and/or otherwise assimilated ormodified.) The device of the present invention may also include abio-incorporable overlay cover for placement over the vacuum dressing toform a sealed enclosure in which sub-atmospheric pressure may beprovided and maintained to the vacuum dressing and the tissue to betreated. The overlay cover may be adherent to the dressing and extendbeyond the vacuum dressing to permit attachment of the overlay cover tosurrounding non-damaged heart tissue. The overlay cover may begelatinous in nature to contour to the heart and may be sufficientlypliable so as not to interfere with cardiac function. The overlay covermay be secured to the myocardium with fibrin glue, mini-staples, orsutures.

In use, the device of the present invention may be placedthoracoscopically over the area of muscle that has infarcted and overthe adjacent zone of stasis. The device may be placed through a smallincision made in the chest wall and perforated through the pericardium.The vacuum dressing may be collapsible in structure such that it can berolled up or folded so as to be small enough for insertion through athoracoscope tube. The epicardium may be perforated with a CO₂ orsimilar laser or other cutting instrument to expose the underlyingischemic myocardium. The vacuum dressing may then be placed directlyover this ischemic area. The overlay cover may also be placed andsecured to surrounding heart tissue endoscopically as well. A vacuumtube, e.g., a small catheter, may then be introduced so that the distalend of the vacuum tube is in gaseous communication with the enclosureunder the overlay cover to supply sub-atmospheric pressure to theenclosure and the tissue to be treated. The other end of the vacuum tubemay then be placed in gaseous communication with a vacuum source toproduce sub-atmospheric pressure, and the vacuum source may be activatedto supply the sub-atmospheric pressure to effect negative pressuretherapy of the damaged heart tissue. In addition, the sub-atmosphericpressure may be supplied intermittently at a rate that is matched to theheart rate.

The present invention may also provide delayed treatment of myocardialinfarction where there is already a stable zone of myocardial celldeath. Again through an endoscope and a small incision in the chestwall, a bio-incorporable vacuum dressing may be placed on the area thatis infarcted. Again, exposure of the myocardium involved and adjacentmyocardium may be required and provided with a CO₂ or similar cuttingdevice to perforate the epicardium. The vacuum dressing may be modifiedso that a lattice of myocardial or peripheral muscle cells may beincorporated within it. The vacuum dressing may also incorporate a smallcatheter with the ability to reinfuse additional myocardial cells,pleuripotent progenitor cells, or peripheral muscle cells at subsequentserial times. In areas where there is near complete cell death or thereis little or no contraction of the muscle cells in the damaged cardiactissue, new contractile cells could be seeded to replace and restore thecontractile function of the damaged cardiac tissue. Initially,peripheral muscle or peripheral muscle cells grown from culture could beused. These cells have a finite life cycle and would be expected tofatigue over time. The myocardium could be biopsied at the time of thetreatment of the initial treatment and myocardial cells removed andcultured to create a larger mass of viable of cells. The harvestedmyocardial cells could be maintained in culture and used for laterperiodic infusion to develop a myocardial patch that would cover thearea of previous infarction. Also, progenitor cells could be harvestedand immediately infused to the area of damaged cardiac tissue, or theycould be grown in culture and periodically infused to the area ofdamaged cardiac tissue with the expectation that they would develop intocardiac myocytes. Over time the introduced cells would be induced toundergo mitosis or self-replication thus increasing the functional massof the heart. The ability to progressively add cells that would beprogressively vascularized is a major step in regenerative medicinewhere presently only a sheet of cells can be expected to survive.

More specifically, in one of its aspects the present invention providesa method for treating damaged cardiac tissue using sub-atmosphericpressure. The method comprises placing a porous material in direct orindirect contact with the damaged cardiac tissue to provide gaseouscommunication between one or more pores of the porous material and thedamaged cardiac tissue. The porous material may comprise at least one ofan electrospun material, a cast material, an open-cell foam, or aprinted material. Alternatively or additionally, the porous material maycomprise a bio-incorporable material. The porous material may include,for example, collagen, chitosan, polycaprolactone, polyglycolic acid,polylactic acid, and combinations thereof. In addition, the porousmaterial may be a polyvinyl alcohol foam which may be disposed in directcontact with the damaged cardiac tissue.

The porous material may be sealed in situ over the damaged cardiactissue to provide a region about the damaged cardiac tissue formaintaining sub-atmospheric pressure at the damaged cardiac tissue. Theporous material may be operably connected with a vacuum source forproducing sub-atmospheric pressure at the damaged cardiac tissue, andthe vacuum source activated to provide sub-atmospheric pressure at thedamaged cardiac tissue. The sub-atmospheric pressure may be maintainedat the damaged cardiac tissue for a time sufficient to reduce edema(thus restoring contractility and compliance), decrease interstitialpressure, remove inflammatory mediators, remove inflammatory amplifiers,modulate intracellular mediators, increase reperfusion and microvascularflow, decrease microvascular plugging, and/or decrease retention ofinflammatory cells within the damaged cardiac tissue. Micro and macrodeformation of the cardiac tissue being treated would increasevasculoneogenesis or the formation of new blood vessels in the ischemictissue. This would increase the survivability of the cardiocytes andultimately improve function of the ischemic portion of the heart. Inaddition, macro and micro deformation of small arterioles alreadyexisting in the heart would result in their physical reorientation intothe areas of ischemic tissue, thus increasing perfusion and ultimatelyfunction.

For example, the sub-atmospheric pressure may be maintained at about25-125 mm Hg below atmospheric pressure. The method may also includelocating a cover, such as a bio-incorporable cover, over damaged cardiactissue and sealing the cover to tissue proximate the damaged cardiactissue, e.g., to non-damaged cardiac tissue, for maintainingsub-atmospheric pressure at the damaged cardiac tissue. The cover may beprovided in the form of a self-adhesive sheet which may be located overthe damaged cardiac tissue. In such a case, the step of sealing thecover may include adhesively sealing and adhering the self-adhesivesheet to tissue surrounding the damaged cardiac tissue to form a sealbetween the sheet and tissue surrounding the damaged cardiac tissue.

In another of its aspects the present invention provides an apparatusfor treating damaged cardiac tissue. The apparatus includes a porousmaterial for treating damaged cardiac tissue having a pore structureconfigured to permit gaseous communication between one or more pores ofthe porous material and the cardiac tissue to be treated. The porousmaterial may include at least one of an electrospun material, a castmaterial, and a printed material. Alternatively or additionally, theporous material may comprise a bio-incorporable material. In suchinstances, it may also be beneficial for the porous material to beformulated in such a manner that the outer edges of the porous materialwould be resorbed or degraded more quickly than the inner portion. Therate of removal (resorption/degradation) of the porous material could bematched to the rate of formation of new tissue. One way to control therate of degradation or resorption is by varying the number of crosslinksintroduced into the porous material.

The apparatus may also include a vacuum source for producingsub-atmospheric pressure; the vacuum source may be disposed in gaseouscommunication with the porous material for distributing thesub-atmospheric pressure to the cardiac tissue. The porous material mayhave, at least at a selected surface of the porous material, poressufficiently small to prevent the growth of tissue therein. In addition,the porous material may have, at least at a selected surface of theporous material, a pore size smaller than the size of fibroblasts andcardiac cells, and may have a pore size at a location other than theselected surface that is larger than that of fibroblasts and cardiaccells. The pore size of the porous material may be large enough to allowmovement of proteins the size of albumin therethrough. Also, the porousmaterial may include at least one surface that is sealed to prevent thetransmission of sub-atmospheric pressure therethrough. The apparatus mayalso include a cover, such as a bio-incorporable cover, configured tocover the damaged cardiac tissue to maintain sub-atmospheric pressureunder the cover at the damaged cardiac tissue.

The bio-incorporable porous material and/or cover may be constructedfrom synthetic materials such as polyglycolic acid, polylactic acid, orpoly-o-citrate, or they can be constructed of naturally occurringmolecules such as collagen, elastin, or proteoglycans. Combinations ofsynthetic molecules, combinations of naturally occurring molecules, orcombinations of synthetic with naturally occurring molecules can be usedto optimize the material properties of the porous material and cover.

An example of a material which may be used to fabricate the porousmaterial is polycaprolactone (PCL). In one exemplary formulation,polycaprolactone is mixed with sodium chloride (1 part caprolactone to10 parts sodium chloride) and placed in a sufficient volume ofchloroform to dissolve the components. The solution is poured into anappropriately sized and shaped container and allowed to dry for twelvehours. The sodium chloride is then leached out in water.

A second exemplary cast formulation for the porous material is chitosan,1.33% (weight/volume) in 2% acetic acid. The solution (20 ml) is pouredinto an appropriately sized container and frozen for 2 hours at −70° C.,then transferred to a lyophylizer and vacuum applied for 24 hours. Thefreeze dried dressing is then crosslinked with 2.5 to 5% glutaraldehydevapor for 12 to 24 hours.

Thus, the present invention provides devices and methods for minimizingthe progression of pathologic processes, minimizing the disruption ofphysiological cardiac integrity, and minimizing the interference withcardiac blood flow and nutrition and increasing revascularization ofischemic areas of the heart by vascular neogenesis and reorientation ofexisting vessels. By decreasing cardiac edema and interstitial pressurethe risk of cardiac cell death and compromise may be minimized. Inaddition, the present invention facilitates the removal of mediators,degradation products, and toxins that enhance the inflammatory andpathophysiological response in the damaged cardiac tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing summary and the following detailed description of thepreferred embodiments of the present invention will be best understoodwhen read in conjunction with the appended drawings, in which:

FIG. 1 schematically illustrates a partial cross-sectional view of anexemplary configuration of an apparatus of the present invention in situprior to the application of sub-atmospheric pressure;

FIG. 2 schematically illustrates the partial cross-sectional view ofFIG. 1 as a sub-atmospheric pressure is being applied;

FIG. 3 schematically illustrates the partial cross-sectional view ofFIG. 1 after sub-atmospheric pressure has been applied;

FIG. 4 schematically represents a cross-sectional view of an exemplaryconfiguration of the present invention in situ in which the tissuesoverlying the heart have been closed around the tube to create a spacecapable of maintaining a vacuum so no overlay cover is required;

FIG. 5 schematically represents a partial cross-sectional view of theapparatus of the present invention in situ in which the porous materialis layered with a smaller pore layer adjacent to the damaged tissue anda layer with larger pores above the smaller pore layer;

FIG. 6 schematically represents a view of an exemplary configuration ofa porous material of the present invention in which only one side of theporous material is open and not sealed;

FIG. 7 schematically represents a cross-sectional view of an exemplaryconfiguration of the present invention in which an overlay cover hasbeen placed over the porous material and potential leaks sealed withfibrin glue;

FIG. 8 schematically represents a partial cross-sectional view of anexemplary configuration of the present invention in which the edges ofthe overlay cover have been turned under;

FIG. 9 schematically represents a cross-sectional view of an exemplaryconfiguration of the present invention in which the overlay cover isself adhesive;

FIG. 10 schematically represents an exemplary configuration of the coverof the present invention in which the tube passes through the overlaycover;

FIG. 11 schematically represents a partial cross-sectional view of thevacuum tube attaching to the overlay cover;

FIG. 12 schematically represents a kidney, with artery and vein;

FIG. 13 schematically represents an open clamshell or bi-valve chamberfor application of sub-atmospheric pressure; and

FIG. 14 schematically represents a kidney disposed within the chamber ofFIG. 13.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the figures, wherein like elements are numbered alikethroughout, the present invention relates to devices and methods thatuse sub-atmospheric (or negative) pressure for treating damaged cardiactissue, where “damaged” tissue is defined to include tissue that isinjured, compromised, or in any other way impaired, such as damage dueto trauma, disease, infection, surgical complication, or otherpathologic process, for example. More specifically, the devices andmethods of the present invention can effect treatment of myocardialinfarction.

An exemplary configuration of a sub-atmospheric cardiac treatment device100 of the present invention may include a vacuum source 30 forsupplying sub-atmospheric pressure via a tube 20 to a porous material10, such as a bio-incorporable porous material, disposed in direct orindirect contact with the damaged cardiac tissue 7, FIGS. 1-4. As usedhere, “indirect contact” is defined to mean placement of an intermediatematerial for transmitting sub-atmospheric pressure in contact with boththe damaged cardiac tissue 7 and the porous material 10. In this regard,the porous material 10 may be structured to deliver and distributesub-atmospheric pressure to the damaged cardiac tissue 7. Alternatively,the porous material 10 may be comprised of a material that needs to beremoved after sub-atmospheric therapy is given, which could require asecond surgery. The cardiac treatment device 100 may be applied to apatient by locating a porous material 10 in contact with the damagedcardiac tissue 7 to provide gaseous communication between one or morepores of the porous material 10 and the damaged cardiac tissue 7. A tube20 may be connected to the porous material 10 at a distal end 22 of thetube 20, and the porous material 10 may be sealed in situ by sutures 8in the skin 1 and subcutaneous tissues 2 to provide a region about thedamaged cardiac tissue 7 for maintaining sub-atmospheric pressure, FIG.4. The proximal end 24 of the tube 20 may be attached to a vacuum source30 to operably connect the porous material 10 to the vacuum source 30for producing sub-atmospheric pressure at the damaged cardiac tissue 7upon activation of the vacuum source 30. Optionally, an overlay cover40, such as a bio-incorporable overlay cover 40, may be located over thedamaged cardiac tissue 7 and sealed proximate the damaged cardiac tissue7 to maintain sub-atmospheric pressure at the damaged cardiac tissue 7.

Turning to FIGS. 1-4 in greater detail, an exemplary configuration of asub-atmospheric pressure cardiac treatment device 100 of the presentinvention is illustrated in partial cross-section with the porousmaterial 10 in contact with the damaged cardiac tissue 7. An overlaycover 40 covers the porous material 10 and may extend onto healthycardiac tissue 6 creating an enclosed space 48. An adhesive 41, such asfibrin glue or other material, may be placed between the overlay cover10 and the healthy cardiac tissue 6. The adhesive 41 may also oralternatively be placed around the periphery of the overlay cover 10 toprevent leaks, and may also be placed around a passthrough 52 where thetube exits from the overlay cover 10 to prevent leaks. FIG. 1 depictsthe device 100 prior to application of sub-atmospheric pressure. FIG. 2depicts the device 100 as sub-atmospheric pressure is being applied, andthe enclosed space 48 decreases in volume as fluid and gas are evacuatedfrom the enclosed space 48 and the overlay cover 40 conforms to theporous material 10. FIG. 3 depicts the device 100 after sub-atmosphericpressure has been applied, with the overlay cover 40 conforming to theshape of the porous material 10.

Turning to FIG. 4 specifically, an exemplary configuration of asub-atmospheric cardiac treatment device 100 of the present invention isillustrated in situ in a patient with surrounding tissues shown inpartial cross-section. The tissues illustrated include the skin 1 andsubcutaneous tissue 2, muscle 3, bone 4, pericardium 5, healthynon-damaged cardiac tissue 6, the damaged cardiac tissue 7, and thepleural tissues 12. To provide access to the damaged cardiac tissue 7, aportion of the pericardium 5 may be missing due to surgical dissectionor injury. A porous material 10, such as an open-cell collagen material,may be placed in the subcutaneous space in contact (direct or indirect)with the cardiac tissue 7 to be treated with sub-atmospheric pressure todecrease edema and interstitial pressure, oxygen radicals, inflammatorymediators, and other molecules which may adversely affect cellularresuscitation or viability within the damaged cardiac tissues to improvephysiologic function, for example. The distal end 22 of the tube 20 mayconnect to the porous material 10 and the tube 20 may exit the bodythrough an incision. The tube 20 may have one or more fenestrations 23in that portion of the tube 20 in contact with the porous material 10,FIG. 6. The tissues between the cardiac tissue 7 up to and including theskin 1 are closed with, for example sutures 8, to create an airtightseal capable of maintaining a vacuum. When sub-atmospheric pressure isapplied, the edges of the incised tissues 1-5 are drawn together and thepleural tissues 12 are drawn toward the porous material to help maintainthe vacuum. The proximal end of the tube 24 may be connected to a vacuumsource 30 and the level of sub-atmospheric pressure controlled by acontroller 32. The vacuum source 30 may include a canister to collectany fluid removed.

The cover 40 may serve to further confine the region about the damagedcardiac tissue 7 at which sub-atmospheric pressure is maintained. Thatis, as illustrated in FIGS. 1-3, 7-9, the cover 40, 50 provides anenclosed space/region 48, 58 about the damaged cardiac tissue 7 underthe cover 40, 50, which can serve to isolate the tissues exterior to thecover 40, 50 from exposure to the sub-atmospheric pressure applied tothe damaged cardiac tissue 7. In contrast, as illustrated in FIG. 4, inthe absence of an overlay cover, sub-atmospheric pressure delivered tothe porous material 10 and damaged cardiac tissue 7 may draw thesurrounding tissues, such as the pericardium 5 and pleural tissues 12,inward towards the tube 20 and porous material 10 along the directionsof the arrows shown in FIG. 4. In this regard the stretched and/or movedtissues, such as pericardium 5 and pleural tissues 12 can help toconfine the applied sub-atmospheric pressure to a region between thepericardium 5 and the damaged cardiac tissue 7. In addition the covers40, 50 may further protect the damaged cardiac tissue 7 from exogenousinfection and contamination beyond the protection already afforded bythe porous material 10 and sutured skin 1 and subcutaneous tissue 2.Likewise, the covers 40, 50 may further protect the damaged cardiactissue 7 from the spread of infections from the surrounding tissues(such as cardiac abscesses and mediastinitis).

To assist in maintaining the sub-atmospheric pressure at the damagedcardiac tissue 7, a flexible overlay cover 40 (FIG. 7), or a selfadhesive flexible overlay cover 50 (FIG. 9) may be provided over thedamaged cardiac tissue 7 to provide a region 48, 58 about the damagedcardiac tissue 7 where sub-atmospheric pressure may be maintained, FIGS.7, 8. Specifically, with reference to FIGS. 7, 8, and 9, an overlaycover 40, 50 may be provided over the damaged cardiac tissue 7 andporous material 10 by adhering the cover 40, 50 to cardiac tissuesproximate the damaged cardiac tissue 7 to define an enclosed region 48,58 about the damaged cardiac tissue 7 and porous material 10. Forinstance, the cover 40 may be glued to cardiac tissue using an adhesive41, such as a fibrin glue. The adhesive 41 may comprise anauto-polymerizing glue and/or may desirably include a filler to providethe adhesive 41 with sufficient bulk to permit the adhesive 41 toconform to the shapes of the potentially irregular surfaces which theadhesive 41 contacts. The adhesive 41 may be provided as a separatecomponent or as a portion of the cover 40. For the flexible overlaycover 40, an outside edge or border of the flexible overlay cover 40 mayeither be rolled away from (or laid flat on) the non-damaged cardiactissue 6 or rolled under (or toward) the damaged cardiac tissue 7, FIGS.7, 8. The adhesive 41 may be placed between the edge of the overlaycover 40 and the healthy cardiac tissue 6 to promote an airtight seal.The adhesive 41 may also be placed around the tube 20 where it exitsthrough the overlay cover 40. Alternatively, a self-adhesive flexibleoverlay cover 50 may be curled out away from the damaged cardiac tissue7 so that the underside of the cover 50 (that side facing the porousmaterial 10) may then contact with the surrounding non-damaged cardiactissue 6, FIG. 9.

In addition to an open-cell collagen material, the porous material 10may also include a polyglycolic and/or polylactic acid material, asynthetic polymer, a flexible sheet-like mesh, an open-cell polymerfoam, a foam section, a porous sheet, a polyvinyl alcohol foam, apolyethylene and/or polyester material, or other suitable materialswhich may be fabricated by electrospinning, casting, or printing, forexample. Such materials include a solution of chitosan (1.33%weight/volume in 2% acetic acid, 20 ml total volume) which may be pouredinto an appropriately sized mold. The solution is then frozen for 2hours at −70° C., and then transferred to the lyophylizer and vacuumapplied for 24 hours. The dressing may be cross-linked by 2.5%-5%glutaraldehyde vapor for 12-24 hours to provide a cast porous material.

Additionally, the porous material 10 may be made by castingpolycaprolactone (PCL). Polycaprolactone may be mixed with sodiumchloride (1 part caprolactone to 10 parts sodium chloride) and placed ina sufficient volume of chloroform to dissolve the components. A desiredamount, e.g., 8 ml, of the solution may be poured into an appropriatelysized and shaped container and allowed to dry for twelve hours. Thesodium chloride may then be leached out in water for 24 hours.

The overlay cover 40 may also be bio-incorporable and may consist of anelectrospun mixture of Type I collagen and poly 1,8-octanediol citrate(POC) (80%:20% weight/weight). The solution concentration may be 15%dissolved in hexafluoro-2 proponal (HFP) with a total volume of 9.5 ml.The solution may then be ejected from a syringe through an 18 gaugeneedle at a flow rate of 1-3 ml/hour. The voltage may be 25 KV with aworking distance of 20-25 cm. The film may then be heat polymerized at80° C. for 48 hours (of 90° C. for 96 hours) and cross-linked in2.5%-10% glutaraldehyde vapor for 24 hours.

It is also possible to use electrospun materials for the porous material10 and cast materials for the overlay cover 40. One example of aformulation and method for making an electrospun porous material 10 is acombination of collagen Type I:chondroitin-6-sulfate (CS):poly1,8-octanediol citrate (POC) in a ratio of 76%:4%:20%: by weight. Twosolvents were utilized for the collagen/CS/POC. The CS was dissolved inwater and the collagen and POC were dissolved in 2,2,2-trifluoroethanol(TFE). A 20% water/80% TFE solution (volume/volume) solution was thenused. For electrospinning, the solution containing the collagen:CS:POCmixture was placed in a 3 ml syringe fitted to an 18 Ga needle. Asyringe pump (New Era Pump Systems, Wantaugh, N.Y.) was used to feed thesolution into the needle tip at a rate of 2.0 ml/hr. A voltage of 10-20kV was provided by a high voltage power supply (HV Power Supply, GammaHigh Voltage Research, Ormond Beach. FL) and was applied between theneedle (anode) and the grounded collector (cathode) with a distance of15-25 cm. The dressings were then cross-linked with glutaraldehyde(Grade II, 25% solution) and heat polymerized (80° C.) for 48 hours. Itis also possible to electrospin collagen Type I dressings starting withan initial concentration of 80 mg/ml of collagen in1,1,1,3,3,3-hexafluoro-2-propanol (HFP), then use the sameelectrospinning conditions as the collagen:CS:POC combination.

Examples of cast overlay cover formulas include the use of 1,8 poly(octanediol) citrate (POC) or other combinations of diol citrates, whichcould be 1,6 hexanediol or 1,10 decanediol, for example. To make thecast overlay cover 40, equimolar amounts of anhydrous citric acid andthe diol of choice may be combined in a round bottom flask. (As anexample: 38.4 g citric acid and 29.2 g octanediol). The solution may beheated in an oil bath for 10 min at 165° C. until melted, then continuedto be heated at 140° C. for 45 min. The polymer may be used in this formalthough unreacted monomers are also present. To remove the unreactedmonomer, equivolume amounts of polymer and 100% acetone may be added toa flask and shaken until the polymer is completely dissolved, thenpoured into an appropriately shaped mold. The acetone may be evaporatedovernight in a chemical hood at room temperature. The films may bepolymerized at 80° C. for 36 hr and then 18 hr at 110° C.

Alternatively, to cast overlay covers 40 of chitosan, a solution of 2%acetic acid in water may be added to 1% chitosan weight/volume. (Forexample 400 μl acetic acid may be added to 20 ml water, then 200 mgchitosan added.) Films may be prepared by pouring the mixture directlyinto the mold and allowing the solution to dry overnight. Cast overlaycovers 40 of poly L (lactic acid) or poly D,L (co-glycolic lactic acid)dissolved in chloroform can also be made by pouring the solution intomolds and evaporating the solvent (chloroform) off.

An additional method for creating porous materials 10 and overlay covers40 is to use thermal inkjet printing technologies. Bio-incorporablematerials such as collagen, elastin, hyaluronic acid, alginates, andpolylactic/polyglycolic acid co-polymers may be printed. As examples,Type I collagen (Elastin Products Co., Owensville, Mo.) dissolved in0.05% acetic acid, then diluted to 1 mg/ml in water can be printed, ascan sodium alginate (Dharma Trading Co., San Raphael, Calif.) 1 mg/ml inwater. A mixture of Type I collagen (2.86 mg/ml in 0.05% acetic acid)and polylactic/polyglycolic acid (PURAC America, Blair, Nebr.) (14.29mg/ml in tetraglycol (Sigma Aldrich, St. Louis Mo.)) can also beprinted. Hardware from a Hewlett Packard 660c printer can be attached toa platform for which the height can be adjusted for printing in layers.With minimal changes to the hardware, no software changes need to bemade.

Turning to FIG. 5, the porous material 10 may comprise layers, with thelayer 112 closest to the damaged cardiac tissue containing poressufficiently small at the interface between the porous material 110 andthe damaged cardiac tissue 7 to prevent the growth of tissue therein,e.g., a pore size smaller than the size of fibroblasts and cardiaccells. Otherwise the porous material 110 may stick to the damagedcardiac tissue 7 and cause bleeding or trauma, and potentially evendisruption of the ventricular wall when the porous material 110 isremoved. Additionally, growth of tissues into the porous material 110may result in eventual erosion through the ventricular wall or pleuraltissues with continual movement and rubbing of the porous material 110against these tissues if the porous material 110 is left in the patient.Further, growth of tissues into the porous material 110 may result innon-contractible scar formation within the porous material or potentialcalcification of tissues within the porous material 110 if the porousmaterial 110 is left within the patient. In addition, the pore size atthe interface between the porous material 10, 110 and the damagedcardiac tissue 7 may be sufficiently small so as to avoid the excessiveproduction of granulation or scar tissue at the damaged cardiac tissue 7which may interfere with the physiologic function of the heart. At thesame time, the pore size of the porous material 10, 110 may be largeenough to allow movement of proteins the size of albumin therethrough topermit undesirable compounds to be removed, such as mediators,degradation products, and toxins.

The porous material 10, 110 may, however, have a larger pore size (e.g.,larger than that of fibroblasts and cardiac cells) interior to theporous material 10, 110 or at any other location of the porous material10 that is not in contact with cardiac tissue 7. For example, the porousmaterial 110 may comprise a multi-layer structure with a non-ingrowthlayer 112 having a sufficiently small pore size to prevent the growth oftissue therein for placement at the cardiac tissue 7, and may have anadditional layer 114 of a different material that has a relativelylarger pore size in contact with the non-ingrowth layer 112.

Alternatively, as depicted in FIG. 6, the porous material 210 may behomogeneous in composition and/or morphology. At a location away fromthe interface with the damaged cardiac tissue, the porous material 210may have a pore size sufficiently large to promote the formation ofgranulation tissue at other tissues in the spaces surrounding thedamaged cardiac tissue, such as promotion of granulation tissue in areaswhere cardiac disruption has occurred. In addition, the porous material210 may have a configuration in which one or more sides or surfaces 212of the porous material 210 are sealed to prevent the transmission ofsub-atmospheric pressure through such a sealed surface 212, while at thesame time having at least one surface 214 through which sub-atmosphericpressure may be transmitted. Such a configuration of the porous material210 can present preferential treatment of tissue on one side of theporous material 210 while not treating tissue on the other side. Forinstance, the damaged cardiac tissue could be treated with thenon-sealed interface on one side 214 of the porous material 210.

In addition, the porous material 10 may comprise a non-metallic materialso that an MRI can be performed while the porous material 10 is in situ.The porous material 10 may also comprise a material that is sufficientlycompliant so that it does not interfere with cardiac function. At thesame time, the porous material 10 may comprise a material that issufficiently firm so that the porous material 10 does not collapse somuch as to create a pull on, or distortion of, the cardiac tissue 6, 7that might interfere with cardiac function.

Turning to FIG. 7, to deliver sub-atmospheric pressure to the porousmaterial 10 for distribution to the damaged cardiac tissue 7, a tube 20may be connected directly or indirectly in gaseous communication withthe porous material 10 at the distal end 22 of the tube 20. For example,the distal end 22 of the tube 20 may be embedded in the porous material10 or may be placed over the porous material 10. The distal end 22 ofthe tube 20 may also include one or more fenestrations 23 to assist indelivering the sub-atmospheric pressure to the porous material 10 andthe damaged cardiac tissue 7. The tube 20 may extend through an openingin the skin 1 and subcutaneous tissue 2 which may be secured about thetube 20 with a suture 8 to assist in providing a seal about the tube 20.The proximal end 24 of the tube 20 may be operably connected to a vacuumsource 30 (e.g., The V.A.C., Model 30015B, Kinetic Concepts, Inc., SanAntonio, Tex.) to provide sub-atmospheric pressure that is transmittedvia the tube 20 to the porous material 10 and the damaged cardiac tissue7.

The vacuum source 30 may include a controller 32 to regulate theproduction of sub-atmospheric pressure. For instance, the vacuum source30 may be configured to produce sub-atmospheric pressure continuously orintermittently; e.g., the vacuum source 30 may cycle on and off toprovide alternating periods of production and non-production ofsub-atmospheric pressure. The duty cycle between production andnon-production may be between 1 to 10 (on/off) and 10 to 1 (on/off). Inaddition, intermittent sub-atmospheric pressure may be applied by aperiodic or cyclical waveform, such as a sine wave, or may be cycledafter initial treatment to mimic a more physiologic state, such as theheart rate. The sub-atmospheric pressure may also be cycled on-offas-needed as determined by monitoring of the pressure in the damagedcardiac tissue 7. In general, the vacuum source 30 may be configured todeliver sub-atmospheric pressure between atmospheric pressure and 200 mmHg below atmospheric pressure to minimize the chance that thesub-atmospheric pressure may result in reduction in localized blood flowdue to either constriction of capillaries and small vessels or due tocongestion (hyperemia) within the damaged cardiac tissue 7 or otherwisebe deleterious to the damaged cardiac tissue 7. The application of sucha sub-atmospheric pressure can operate to remove edema from the damagedcardiac tissue 7, thus preserving cardiac function to increase theprobability of recovery and survival in a more physiologically preservedstate.

Turning to FIG. 10, sub-atmospheric pressure may be delivered under thecover 50 by cooperation between the cover 50 and the tube 20.Specifically, the flexible overlay cover 40 (or self-adhesive flexibleoverlay cover 50) may include a passthrough 52 through which the distalend 22 of the tube 20 passes to provide gaseous communication betweenthe tube 20 and the space under the flexible overlay cover 40 over thedamaged cardiac tissue.

In another of its aspects, the present invention also provides a methodfor treating damaged cardiac tissue using sub-atmospheric pressure with,by way of example, the devices illustrated in FIGS. 1-4. In particular,the method may comprise locating a porous material 10 proximate thedamaged cardiac tissue 7 to provide gaseous communication between one ormore pores of the porous material 10 and the damaged cardiac tissue 7.The porous material 10 may be sealed in situ proximate the damagedcardiac tissue 7 to provide a region about the damaged cardiac tissue 7for maintaining sub-atmospheric pressure at the damaged cardiac tissue7. In this regard, the muscles 3, and bone 4 may be looselyre-approximated over top of the porous material 10 with the tube 20exiting through the skin 1 and subcutaneous tissue 2 and the skin 1 andsubcutaneous tissue 2 sutured closed. A further airtight dressing mayoptionally be placed over the suture site to promote an airtight seal.The porous material 10 may be operably connected with a vacuum source 30for producing sub-atmospheric pressure at the damaged cardiac tissue 7,and the vacuum source 30 activated to provide sub-atmospheric pressureat the damaged cardiac tissue 7. For example, the sub-atmosphericpressure may be maintained at about 25 to 125 mm Hg below atmosphericpressure. The sub-atmospheric pressure may be maintained at the damagedcardiac tissue 7 for a time sufficient to decrease edema at the damagedcardiac tissue 7. In addition, the sub-atmospheric pressure may bemaintained at the damaged cardiac tissue 7 for a time sufficient toprepare the cardiac tissue 7 to achieve a stage of healing anddiminution of edema and inflammatory mediators or amplifiers. The methodmay be used for at least 2 hours, or can be used for many days. At theend of the vacuum treatment, the sutures 8 may be removed and the skin1, subcutaneous tissue 2, muscles 3 and bone 4 re-opened. The porousmaterial 10 may then be removed and the skin 1, subcutaneous tissue 2,and/or muscles 3 re-sutured closed.

The method may also include locating an overlay cover 40, 50, such as abio-incorporable cover 40, 50, over the damaged cardiac tissue 7 andsealing the overlay cover 40, 50 to tissue proximate the damaged cardiactissue 7 for maintaining sub-atmospheric pressure at the damaged cardiactissue 7. The step of sealing the overlay cover 40, 50 to tissuesurrounding the damaged cardiac tissue 7 may comprise adhesively sealingand adhering the overlay cover 40, 50 to tissue surrounding the damagedcardiac tissue 7. The overlay cover 50 may be provided in the form of aself-adhesive sheet 50 which may be located over the damaged cardiactissue 7. In such a case, the step of sealing the overlay cover 50 mayinclude adhesively sealing and adhering the self-adhesive overlay cover50 to non-damaged cardiac tissue 6 surrounding the damaged cardiactissue 7 to form a seal between the overlay cover 50 and the non-damagedcardiac tissue 6 surrounding the damaged cardiac tissue 7. In addition,the step of operably connecting a vacuum source 30 in gaseouscommunication with the porous material 10 may comprise connecting thevacuum source 30 to the tube 20 which attaches to the vacuum port 42 ofthe cover 140 FIG. 11.

In still another aspect of the present invention, in addition to injuredtissues and organs, the devices and methods may also be used to increasethe size and function of diseased or damaged organs. For example, thesize of a partially functioning kidney may be increased to a sizesufficient to return the total filtering capacity to normal levels,FIGS. 12-14, such as the increase in size of the remaining kidney 301 asis observed in patients who only have one functioning kidney 301. Insuch a situation, a rigid or semi-rigid bi-valved enclosure 304 with anopening 305 for the vascular pedicle may be placed around the kidney301. When the bi-valved enclosure 304 is closed, the area where the twohalves meet creates an air tight seal. The vascular pedicle enters(artery 302) and exits (vein 303) through the opening 305. Fibrin glue306 or other biocompatible sealant may be placed around the artery 302and vein 303 at the site of the opening 305 to create an airtight seal.The enclosure 304 may include a second opening 305 or a nipple 308. Atube 309 may be inserted through the second opening 305 or attached tothe nipple 308. The tube 309 may exit through the skin, be connected toa collection vessel, and then connected to a vacuum source. A controlledvacuum of up to 125 mm Hg sub-atmospheric pressure may be applied eitherintermittently, with an ‘on’ time of up to five minutes and an ‘off’time of up to 10 minutes. Alternatively, the vacuum may be applied in aperiodic or cyclical manner, such as a sine wave, in which the absolutevalue of the lower (closest to atmospheric pressure) values of theapplied vacuum are less than the diastolic blood pressure to allow bloodto flow out of the treated organ. The time in which the applied vacuumis greater (in absolute value) than the diastolic blood pressure may beup to five minutes, with the time in which the applied vacuum is lower(in absolute value) than the diastolic blood pressure may be up to tenminutes. The technique is continued until the treated organ has eitherreached the desired level of function or fills the container. As anadditional example, this device and technique may similarly be used onlobes of the liver or for increasing the size of the pancreas.

EXAMPLES Example 1

The porcine heart has anatomy similar to that of humans with the mainvasculature consisting of the right and left coronary arteries. The leftmain coronary artery splits into the circumflex coronary artery and theleft anterior descending (LAD) coronary artery. The LAD runs down alongthe anterior septum and perfuses the anterior portion of the leftventricle with diagonal branches. For these studies, a porcine model ofischemia-reperfusion was used that included the temporary ligation of2-3 diagonal branches of the LAD in order to create an ischemic area onthe anterior portion of the heart. These coronary arteries were occludedfor 75 minutes and then reperfused for 3 hours to allow forischemia/reperfusion injury to develop. The negative pressure therapywas applied only during the reperfusion phase of the experiments tosimulate a clinically relevant treatment window.

To begin the study, the animals were sedated and transported to theoperating room. The first 13 animals had the heart exposed through athoracotomy, all subsequent animals had the heart exposed through asternotomy. The 2-3 diagonal branches of the LAD were ligated (occludedwith suture) in order to create an ischemic area on the anterior portionof the heart. These coronary arteries were occluded for 75 minutes andthen reperfused for 3 hours to allow for reperfusion injury to develop.The negative pressure therapy was applied only during the reperfusionphase of the experiments to simulate a clinically relevant treatmentwindow. Five control animals were created from the first 13 animals ofthe study.

Following successful completion of control animals to validate the studydesign, the subsequent 5 successful (sternotomy) animals had negativepressure therapy treatment to the ischemic area of the heart for 3 hoursduring the reperfusion time. For the first 5 successfully treatedanimals, the vacuum dressing included use of a polyvinyl alcohol porousmaterial (Versafoam, KCl, San Antonio Tex.), cut to approximately 1 mmthickness and trimmed to match the ischemic area. The evacuation tubewas either embedded into a slit cut into the porous material (2animals), or was sutured to the outer surface of the porous material (3animals). This vacuum dressing was then covered with a biologicallyderived overlay cover. These biological coverings included: 1 animaltreated with E•Z DERM™ (Non-perforated porcine biosynthetic wounddressing, Brennen Medical, St. Paul, Minn.); 1 animal treated withbovine pericardium; and 3 animals treated with AlloDerm® (human dermis)(LifeCell). The overlay covers were attached to the heart by threemeans: suturing, fibrin glue, and self sealing due to a relatively large‘apron’ of the cover material around the periphery of the vacuumdressing. The evacuation tube exited from under the edge of the ‘apron’of the overlay covers. The fibrin glue was used in conjunction withsuturing and also with spot sealing for the self sealing application (atwrinkles, where the evacuation tube exited, etc.). Negative pressure of125 mm Hg (i.e., 125 mm Hg below atmospheric) was then applied for 3hours during the reperfusion period using The V.A.C., Model 30015B,Kinetic Concepts, Inc., San Antonio, Tex.

To determine the effects of ischemia/reperfusion, the sutures werere-tied at the end of the 3 hour reperfusion period. Blue dye (patentblue, Sigma-Aldrich Inc, St. Louis, Mo.) was injected into the rightatrium. This stained the areas of the heart that were normally perfused.The left ventricle was dissected free from the rest of the heart andweighed (LV in Table). The area of ischemia (non-blue area) was furtherdissected from the left ventricle. The blue area of the left ventriclewas then weighed (Blue in Table). The ischemic area (non-blue tissue)was then stained with a dye (2,3,5-triphenyltetrazolium chloride,Sigma-Aldrich Inc., St Louis Mo.) which stains live cells red. The redareas were dissected from the area of ischemia and were weighed (Red inTable), leaving areas of pale dead tissue (area of necrosis—AN inTable), and these pale tissue samples were weighed (Pale in Table). Thecombined Red and Pale areas constitute the area at risk (AAR in Table).The AN/AAR is the size of the infarct (percent of tissue that diedduring the ischemia/reperfusion time periods).

The results for the 5 control animals were:

TABLE 1 Control Animals AAR/ AN/ Pale LV AAR Blue Red (AN) LV AAR (%)(%) Animal 1 75.6 5.85 2.18 83.63 8.03 9.60 27.15 Animal 2 90.5 10.632.44 103.57 13.07 12.62 18.67 Animal 3 85.39 12.16 4.26 101.81 16.4216.13 25.94 Animal 4 92.45 8.17 3.47 104.09 11.64 11.18 29.81 Animal 581.24 9.86 4.34 95.44 14.20 14.88 30.56 Mean 97.71 12.67 12.88 26.43 StdDev 8.59 3.13 2.66 4.73 N 5.00 5.00 5.00 5.00 Std Err 3.84 1.40 1.192.12

The results for the 5 treated animals were:

TABLE 2 −125 mmHg Treated Animals AAR/ AN/ LV AAR Group Blue Red Pale LVAAR (%) (%) Animal 1 73.06 10.31 1.23 84.60 11.54 13.64 10.66 Animal 273.2 5.9 0.61 79.71 6.51 8.17 9.37 Animal 3 75 11.15 2.05 88.20 13.2014.97 15.53 Animal 4 54.1 4.85 0.52 59.47 5.37 9.03 9.68 Animal 5 62.128.63 1.42 72.17 10.05 13.93 14.13 Mean 76.83 9.33 11.95 11.87 Std Dev11.41 3.32 3.11 2.78 N 5.00 5.00 5.00 5.00 Std Err 5.10 1.48 1.39 1.24

Thus, the mean sizes of the infarct (AN/AAR; percent of tissue that diedduring the ischemia/reperfusion time period) for the control and treatedanimals were:

Control 26.43+/−2.12% (mean+/−SEM) (n=5)

Treated 11.87+/−1.24% (mean+/−SEM) (n=5),

with T-test results of P<0.001 for infarct size and P<0.625 for area atrisk.

Example 2

Another experiment was conducted using 50 mm Hg vacuum for treatment forcomparison to original control animals from Example 1 above. Thesurgical technique in this experiment was similar to that used for thoseof Example 1. These animals were sedated and prepped for surgery. Theheart was exposed through a midline sternotomy. Branches of the leftanterior descending artery were ligated for 75 minutes. A polyvinylalcohol vacuum dressing was placed over the ischemic area and anAlloDerm® cover was placed over the vacuum dressing and sealed intoplace with a combination of sutures and fibrin glue. Negative pressureof 50 mm Hg was applied for 3 hours. At the end of this time the heartwas stained for area of risk, removed and then counter stained for areaof necrosis. The infarct size results for these five, 50 mm Hg negativepressure therapy animals were significantly smaller (P<0.001) than forthe control animals. The infarct size for the 50 mm Hg treated animalswas smaller than the infarct size for the 125 mm Hg treated animals, butwas not significantly smaller.

Group AAR/LV (%) AN/AAR Control 12.9 ± 1.2 26.4 ± 2.1   50 mmHg negative11.8 ± 2.0  9.3 ± 1.8** pressure 125 mmHg negative 11.9 ± 1.4  11.9 ±1.2** pressure **p < 0.001 compared to Control animals

The mean arterial pressure and heart rate of animals in all three groups(control, −125 mm Hg, −50 mm Hg) were comparable during the course ofthese experiments.

Fifteen micron neutron-activated microspheres (BioPAL, Inc, Worcester,Mass.) were injected into the left atrium at baseline, end of ischemia,30 minutes into reperfusion and at 180 minutes of reperfusion (end ofthe experiment). A reference sample of arterial blood was simultaneouslydrawn from the femoral artery at a rate of 7 mL per minute for ninetyseconds. Following infarct sizing procedures, tissue samples from thenon-ischemic (blue tissue), ischemic non-necrotic (red tissue), andischemic necrotic areas (pale tissue) were collected and sent to themanufacturer for blood flow analysis (BioPAL, Inc., Worchester, Mass.).Blood flow was calculated as [(FR×CPMT)/CPMR)/tissue weight in grams,where FR=reference sample flow rate (7 mL/min), CPMT=counts per minutein tissue samples and CPMR=counts per minute in the reference bloodsample. Blood flow is reported as mL/min/gram tissue.

Analysis of blood flow reveals that both treated groups had similarbaseline blood flows in all 3 regions. In the normally perfusednon-ischemic zone, blood flow remained relatively constant throughoutthe experiment with no significant group or time related differences.(Table 3) In the ischemic, non-necrotic (red) and ischemic, necroticzones (pale), ischemia was characterized by an equivalent and nearlycomplete loss of blood flow among all three groups. These zones alsoexhibited normal reactive hyperemia (30 minutes after reperfusion), andblood flow that returned approximated baseline flow levels by the end ofthe 3 hour reperfusion time. (Table 4).

TABLE 3 Blood flow (ml/minute/gram tissue) from microsphere analysisBaseline Control −125 mmHg −50 mmHg Animal blue Red Pale blue Red Paleblue Red Pale 1 — — — 0.36 0.328 0.333 0.596 1.1 0.77 2 1.072 0.7090.716 0.308 0.401 0.448 0.474 0.321 0.551 3 0.378 0.347 0.505 0.3920.411 0.353 0.531 0.444 0.422 4 0.577 0.729 0.599 0.643 1.32 0.82 0.6250.629 0.699 5 0.376 0.495 0.412 0.423 0.687 0.482 0.393 0.57 0.596 Mean0.603 0.57 0.558 0.4252 0.629 0.487 0.524 0.613 0.608 SD 0.33 0.18 0.130.13 0.41 0.20 0.09 0.30 0.13 N 4 4 4 5 5 5 5 5 5 SEM 0.16 0.09 0.070.06 0.18 0.09 0.04 0.13 0.06 During Occlusion Control −125 mmHg −50mmHg Animal Blue Red pale blue Red pale blue Red pale 1 — — — 0.3450.065 0.012 0.387 0.056 0.025 2 1.031 0.073 0.0255 0.335 0.064 0.0290.352 0.008 0.029 3 0.3 0.016 0.022 1.196 0.06 0.051 0.714 0.024 0.041 40.428 0.129 0.017 0.454 0.084 0.071 0.494 0.038 0.035 5 0.4 0.024 0.0110.509 0.054 0.029 0.441 0.037 0.1 Mean 0.540 0.061 0.0189 0.568 0.0650.038 0.478 0.033 0.046 SD 0.33 0.05 0.01 0.36 0.01 0.02 0.14 0.02 0.03N 4 4 4 5 5 5 5 5 5 SEM 0.17 0.03 0.00 0.16 0.01 0.01 0.06 0.01 0.01Reperfusion 30 minutes Control −125 mmHg −50 mmHg Animal blue red paleblue Red pale blue red pale 1 — — — 0.379 1.341 1.022 0.441 1.355 2.3612 1.102 1.522 1.872 0.37 0.559 0.692 0.402 0.628 0.708 3 0.348 0.540.286 0.298 0.878 0.6 0.741 1.699 1.626 4 0.439 1.054 1.225 1.439 0.9091.288 0.603 1.126 1.477 5 0.496 1.272 1.4 — — — 0.676 1.866 1.147 Mean0.596 1.097 1.196 0.622 0.922 0.901 0.573 1.335 1.464 SD 0.34 0.42 0.670.55 0.32 0.32 0.15 0.49 0.61 N 4 4 4 4 4 4 5 5 5 SEM 0.17 0.21 0.330.27 0.16 0.16 0.07 0.22 0.27 Reperfusion 180 minutes Control −125 mmHg−50 mmHg Animal blue red pale blue Red Pale blue red Pale 1 — — — 0.4040.367 0.795 0.467 0.385 0.837 2 1.102 1.522 1.872 0.291 0.365 0.6 0.5930.186 0.649 3 0.348 0.54 0.286 0.38 0.303 0.515 0.804 0.649 0.699 40.439 1.054 1.225 0.513 0.449 0.845 0.912 0.803 0.946 5 0.496 1.272 1.40.53 0.477 0.76 0.483 0.471 0.495 Mean 0.596 1.097 1.196 0.424 0.3920.703 0.652 0.499 0.725 SD 0.34 0.42 0.67 0.10 0.07 0.14 0.20 0.24 0.17N 4 4 4 5 5 5 5 5 5 SEM 0.17 0.21 0.33 0.04 0.03 0.06 0.09 0.11 0.08

TABLE 4 Regional Myocardial blood flow (mL/min/100 g tissue) Control −50mmHg −125 mmHg Blue Red Pale Blue Red Pale Blue Red Pale Baseline 0.60 ±0.16 0.57 ± 0.09 0.56 ± 0.07 0.52 ± 0.04 0.61 ± 0.13 0.61 ± 0.06 0.43 ±0.06 0.63 ± 0.18 0.49 ± 0.09 Occlusion 0.54 ± 0.17 0.06 ± 0.03^(†) 0.02± 0.00^(†) 0.48 ± 0.06 0.03 ± 0.01^(†) 0.05 ± 0.01^(†) 0.57 ± 0.16 0.07± 0.01^(†) 0.04 ± 0.01 R30 0.60 ± 0.17 1.10 ± 0.21  1.2 ± 0.33^(†) 0.57± 0.07 1.33 ± 0.22^(†) 1.46 ± 0.27*^(†) 0.62 ± 0.27 0.92 ± 0.16^(†) 0.90± 0.16 R180 0.41 ± 0.04 1.39 ± 0.35^(†) 0.95 ± 0.16 0.65 ± 0.09 0.50 ±0.11 0.73 ± 0.08 0.42 ± 0.04 0.39 ± 0.03 0.70 ± 0.06* Regionalmyocardial blood flow was determined in 3 regions of the heart: 1)non-ischemic left ventricle; 2) ischemic, non-necrotic left ventricle;3) necrotic left ventricle. *p < 0.05 vs Control within a time periodand within tissue area; ^(†)p < 0.05 vs. Baseline within group andtissue area.

Example 3

A subsequent study was performed to examine resorbable vacuum dressingsand overlay covers. One animal was sedated, prepared for surgery asdescribed, and the heart exposed through a mid-line sternotomy. Branchesof the LAD were ligated for 90 minutes. The dressing was prepared byfreeze drying. A solution of chitosan (1.33% weight/volume in 2% aceticacid, 20 ml total volume) was poured into an appropriately sized mold.The solution was frozen for 2 hours at −70° C., then transferred to thelyophylizer for 24 hours. The dressing was cross-linked by 2.5%glutaraldehyde vapor for 12 hours to provide a porous material. Theoverlay cover was an electrospun mixture of Type I collagen and poly1,8-octanediol citrate (POC) (80%:20% weight/weight). The solutionconcentration was 15% dissolved in hexafluoro-20proponal (HFIP) with atotal volume of 9.5 ml. The solution was ejected from a syringe throughan 18 gauge needle at a flow rate of 3 ml/hour. The voltage was 25 KVwith a working distance of 25 cm. The film was then heat polymerized at80° C. for 48 hours and cross-linked in 2.5% glutaraldehyde vapor for 24hours. The overlay cover was able to maintain the vacuum for theduration of the experiment. However, the vacuum dressing did notdistribute the vacuum equally throughout the dressing due to collapseand flow of the material under vacuum.

Example 4

A further study was performed to test variations of the overlay cover.Three animals were sedated and the heart exposed through a midlinesternotomy. No infarct was created in this study of materials. Theoverlay cover was created similar to Example 3, but with variations,including changes in voltage, flow rate, and concentration ofglutaraldehyde vapor for cross-linking. For these animals, the porousmaterial vacuum dressing was formed from a solution of 80% Type Icollagen/20% POC, 12% total concentration in 8.5 ml HFIP was used. Theflow rate was 2 ml/hour, with the fluid ejected through an 18 gaugeneedle at 35 KV with a working distance of 25 cm. The film was heatpolymerized at 80° C. for 48 hours, then cross-linked with exposure to5% glutaraldehyde vapor for 24 hours. The evacuation tube was sutured toa thin polyvinyl alcohol dressing. The dressing was placed over aportion of the left ventricle and tacked in place with 2-4 sutures. Theoverlay cover was placed over the dressing and fibrin glue was placedaround the edges of the overlay cover to insure a vacuum seal. 50 mm Hgwas applied continuously to the dressing. For two animals a small airleak developed after approximately 2.5 hours, the source of the leak wasnot identified despite a diligent search for the source. The source ofthe leak could have been at the site of a wrinkle in the overlay cover,a tail of the suture material could have punctured a hole in the overlaycover, fluid collecting in the pericardial sack could have ‘floated’ asmall portion of the cover off the heart tissue, etc. For the thirdanimal, the negative pressure was maintained for the duration of thestudy (4 hours application of negative pressure).

Example 5

Two animals were used to test the dressing. The surgical technique wassimilar to that used above. These animals were sedated, prepped forsurgery and the heart exposed through an midline sternotomy. Branches ofthe left anterior descending artery were ligated for 75 minutes. Adressing was made by casting polycaprolactone (PCL). Polycaprolactonewas mixed with sodium chloride (1 part caprolactone to 10 parts sodiumchloride) and placed in a sufficient volume of chloroform to dissolvethe components. 8 ml of the solution was poured into an appropriatelysized and shaped container and allowed to dry for twelve hours. Thesodium chloride was then leached out in water for 24 hours. The dressingwas cut to the size of the ischemic area. The evacuation tube wassutured to the dressing and the dressing placed over the ischemic areaand tacked into place. At the end of the 75 minutes of ischemia thetissue was reperfused. The dressing was covered with AlloDerm® andfibrin glue was placed around the edges of the AlloDerm®. 50 mm Hgvacuum was applied for 3 hours. At the end of this time the heart wasstained for area of risk, removed and then counter stained for area ofnecrosis as described for Examples 1 and 2. For the first animal, thearea at risk (ischemic area, AAR) was fairly small at 7.9% of the leftventricle (LV). The infarct size (area of necrosis divided by area atrisk (AN/AAR×100%) was very small at 2.6% of the area at risk. For thesecond animal, the area at risk was larger at 14.3% (AAR/LV), with aninfarct size (AN/AAR) of 11.52%.

These and other advantages of the present invention will be apparent tothose skilled in the art from the foregoing specification. Accordingly,it will be recognized by those skilled in the art that changes ormodifications may be made to the above-described embodiments withoutdeparting from the broad inventive concepts of the invention. It shouldtherefore be understood that this invention is not limited to theparticular embodiments described herein, but is intended to include allchanges and modifications that are within the scope and spirit of theinvention as set forth in the claims.

1. A method for treating damaged cardiac tissue using sub-atmosphericpressure, comprising: i. placing a porous material proximate the damagedcardiac tissue to provide gaseous communication between one or morepores of the porous material and the damaged cardiac tissue, the porousmaterial comprising at least one of an electrospun material, a castmaterial, an open-cell foam, and a printed material; ii. sealing theporous material in situ over the damaged cardiac tissue to provide aregion about the damaged cardiac tissue for maintaining sub-atmosphericpressure at the damaged cardiac tissue; iii. operably connecting avacuum source in gaseous communication with the porous material forproducing sub-atmospheric pressure at the damaged cardiac tissue; andiv. activating the vacuum source to provide sub-atmospheric pressure atthe damaged cardiac tissue.
 2. The method for treating damaged cardiactissue according to claim 1, wherein the porous material comprises abio-incorporable material.
 3. The method for treating damaged cardiactissue according to claim 2, wherein the rate of bio-incorporation ofthe dressing is higher at the periphery of the dressing than at thecenter of the dressing.
 4. The method for treating damaged cardiactissue according to claim 1, wherein the porous material comprises apolyethylene, polyurethane and/or polyester material.
 5. The method fortreating damaged cardiac tissue according to claim 1, wherein the stepof placing a porous material proximate the damaged cardiac tissuecomprises placing a polyvinyl alcohol foam in direct contact with thedamaged cardiac tissue.
 6. A method for treating damaged cardiac tissueusing sub-atmospheric pressure, comprising: i. placing a porousbio-incorporable material proximate the damaged cardiac tissue toprovide gaseous communication between one or more pores of the porousmaterial and the damaged cardiac tissue; ii. sealing the porous materialin situ over the damaged cardiac tissue to provide a region about thedamaged cardiac tissue for maintaining sub-atmospheric pressure at thedamaged cardiac tissue; iii. operably connecting a vacuum source ingaseous communication with the porous material for producingsub-atmospheric pressure at the damaged cardiac tissue; and iv.activating the vacuum source to provide sub-atmospheric pressure at thedamaged cardiac tissue.
 7. The method for treating damaged cardiactissue according to claim 6, wherein the rate of bio-incorporation ofthe dressing is higher at the periphery of the dressing than at thecenter of the dressing.
 8. The method for treating damaged cardiactissue according to claim 1 or 6, wherein the porous material comprisesmyocardial, peripheral muscle cells, or combinations thereof.
 9. Themethod for treating damaged cardiac tissue according to claim 1 or 6,wherein the step of operably connecting a vacuum source comprisesconnecting a tube between the vacuum source and the porous material, thetube having a distal end in contact with the porous material.
 10. Themethod for treating damaged cardiac tissue according to claim 1 or 6,wherein the step of placing a porous material proximate the damagedcardiac tissue comprises placing the porous material in direct contactwith the damaged cardiac tissue.
 11. The method for treating damagedcardiac tissue according to claim 10, wherein the porous materialcomprises an open-cell foam.
 12. The method for treating damaged cardiactissue according to claim 1 or 6, wherein the step of placing a porousmaterial proximate the damaged cardiac tissue comprises placing theporous material in indirect contact with the damaged cardiac tissue bylocating a porous intermediate material between the porous material andthe damaged heart tissue, with the porous intermediate material disposedin contact with both the porous material and the damaged heart tissue.13. The method for treating damaged cardiac tissue according to claim12, wherein the porous material comprises an open-cell foam.
 14. Themethod for treating damaged cardiac tissue according to claim 1 or 6,wherein the step of sealing porous material in situ comprises locating acover over damaged cardiac tissue and sealing the cover to cardiactissue proximate the damaged cardiac tissue for maintainingsub-atmospheric pressure at the damaged cardiac tissue.
 15. The methodfor treating damaged cardiac tissue according to claim 14, wherein thecover comprises a vacuum port for receiving sub-atmospheric pressurefrom the vacuum source, and wherein the step of operably connecting avacuum source in gaseous communication with the porous materialcomprises connecting the vacuum source with the vacuum port.
 16. Themethod for treating damaged cardiac tissue according to claim 14,wherein the step of sealing the cover to tissue surrounding the damagedcardiac tissue comprises adhesively sealing and adhering the cover tocardiac tissue surrounding the damaged cardiac tissue.
 17. The methodfor treating damaged cardiac tissue according to claim 14, wherein thestep of locating a cover comprises locating a self-adhesive sheet overthe damaged cardiac tissue, and wherein the step of sealing the covercomprises adhesively sealing and adhering the self-adhesive sheet tocardiac tissue surrounding the damaged cardiac tissue to form a sealbetween the sheet and surrounding cardiac tissue.
 18. The method fortreating damaged cardiac tissue according to claim 14, wherein the stepof locating a cover comprises locating a bio-incorporable cover over thedamaged cardiac tissue.
 19. The method for treating damaged cardiactissue according to claim 14, wherein the cover comprises an electrospunmaterial.
 20. The method for treating damaged cardiac tissue accordingto claim 14, wherein the cover comprises a cast material.
 21. The methodfor treating damaged cardiac tissue according to claim 14, wherein thecover comprises collagen.
 22. The method for treating damaged cardiactissue according to claim 19, wherein the cover comprises collagen. 23.The method for treating damaged cardiac tissue according to claim 14,wherein the cover comprises a diol citrate.
 24. The method for treatingdamaged cardiac tissue according to claim 19 wherein the cover comprisesa diol citrate.
 25. The method for treating damaged cardiac tissueaccording to claim 14, wherein the cover comprises poly 1,8-octanediolcitrate.
 26. The method for treating damaged cardiac tissue according toclaim 19, wherein the cover comprises poly 1,8-octanediol citrate. 27.The method for treating damaged cardiac tissue according to claim 14,wherein the cover comprises chitosan.
 28. The method for treatingdamaged cardiac tissue according to claim 19, wherein the covercomprises chitosan.
 29. The method for treating damaged cardiac tissueaccording to claim 14, wherein the cover comprises polylactic acid. 30.The method for treating damaged cardiac tissue according to claim 19,wherein the cover comprises polylactic acid.
 31. The method for treatingdamaged cardiac tissue according to claim 1 or 6, comprising maintainingthe sub-atmospheric pressure at the damaged cardiac tissue for a timesufficient to decrease edema in the damaged cardiac tissue.
 32. Themethod for treating damaged cardiac tissue according to claim 1 or 6,comprising maintaining the sub-atmospheric pressure at the damagedcardiac tissue for a time sufficient to decrease mediators, degradationproducts, and/or toxins that enhance the inflammatory andpathophysiological response in the damaged cardiac tissue.
 33. Themethod for treating damaged cardiac tissue according to claim 1 or 6,comprising maintaining a sub-atmospheric pressure of about 25 mm Hgbelow atmospheric pressure at the damaged cardiac tissue.
 34. The methodfor treating damaged cardiac tissue according to claim 1 or 6,comprising maintaining sub-atmospheric pressure of between about 25 and125 mm Hg below atmospheric pressure at the damaged cardiac tissue. 35.The method for treating damaged cardiac tissue according to claim 1 or6, wherein the step of placing a porous material comprises placing aporous material having pores sufficiently small to prevent the ingrowthof tissue therein.
 36. The method for treating damaged cardiac tissueaccording to claim 35, wherein the step of placing a porous materialcomprises placing a porous material having a pore size smaller than thesize of fibroblasts.
 37. The method for treating damaged cardiac tissueaccording to claim 1 or 6, wherein the porous material comprisescollagen.
 38. The method for treating damaged cardiac tissue accordingto claim 1 or 6, wherein the porous material comprises chitosan.
 39. Themethod for treating damaged cardiac tissue according to claim 1 or 6,wherein the porous material comprises polycaprolactone.
 40. The methodfor treating damaged cardiac tissue according to claim 1 or 6, whereinthe porous material comprises a polyglycolic and/or polylactic acid. 41.The method for treating damaged cardiac tissue according to claim 1 or6, wherein the porous material comprises a porous, open-cell collagenmaterial.
 42. The method for treating damaged cardiac tissue accordingto claim 1 or 6, wherein the porous material comprises a poroussynthetic polymer material.
 43. The method for treating damaged cardiactissue according to claim 1 or 6, wherein the porous material comprisesat least one of a porous sheet and a flexible, sheet-like mesh.
 44. Themethod for treating damaged cardiac tissue according to claim 1 or 6,wherein the porous material comprises two or more layers, with the layerclosest to the damaged cardiac tissue containing pores sufficientlysmall at the interface between the porous material and the damagedcardiac tissue to prevent the growth of tissue therein.
 45. The methodfor treating damaged cardiac tissue according to claim 44, wherein theporous material comprises a pore size sufficiently large to promote theformation of granulation tissue at other tissues in the spacessurrounding the damaged cardiac tissue.
 46. The method for treatingdamaged cardiac tissue according to claim 1 or 6, wherein the porousmaterial comprises pores sufficiently small at the interface between theporous material and the damaged cardiac tissue to prevent the growth oftissue therein.
 47. The method for treating damaged cardiac tissueaccording to claim 1 or 6, wherein the porous material comprises a poresize large enough to allow movement of proteins the size of albumintherethrough to permit undesirable compounds to be removed.
 48. Themethod for treating damaged cardiac tissue according to claim 1 or 6,wherein the porous material is sealed to prevent the transmission ofsub-atmospheric pressure on all surfaces but one.
 49. The method fortreating damaged cardiac tissue according to claim 1 or 6, comprisinginfusing peripheral muscle cells into the damaged cardiac tissue. 50.The method for treating damaged cardiac tissue according to claim 1 or6, comprising infusing myocardial cells into the damaged cardiac tissue.51. The method for treating damaged cardiac tissue according to claim 1or 6, comprising infusing pleuripotent progenitor cells into the damagedcardiac tissue.
 52. An apparatus for treating damaged cardiac tissue,comprising: a porous material for treating damaged cardiac tissue havinga pore structure configured to permit gaseous communication between oneor more pores of the porous material and the cardiac tissue to betreated, the porous material comprising at least one of an electrospunmaterial, a cast material, and a printed material; and a vacuum sourcefor producing sub-atmospheric pressure disposed in gaseous communicationwith the porous material for distributing the sub-atmospheric pressureto the cardiac tissue to be treated.
 53. The apparatus according toclaim 52, wherein the porous material comprises a bio-incorporablematerial.
 54. The apparatus according to claim 53, wherein the rate ofbio-incorporation of the dressing is higher at the periphery of thedressing than at the center of the dressing.
 55. The apparatus accordingto claim 52, wherein the porous material comprises a polyethylene,polyurethane, and/or polyester material.
 56. An apparatus for treatingdamaged cardiac tissue, comprising: a porous bio-incorporable materialfor treating damaged cardiac tissue having a pore structure configuredto permit gaseous communication between one or more pores of the porousmaterial and the cardiac tissue to be treated; and a vacuum source forproducing sub-atmospheric pressure disposed in gaseous communicationwith the porous material for distributing the sub-atmospheric pressureto the cardiac tissue to be treated.
 57. The apparatus according toclaim 56, wherein the porous material comprises an open-cell foam. 58.The apparatus according to claim 56, wherein the rate ofbio-incorporation of the dressing is higher at the periphery of thedressing than at the center of the dressing.
 59. The apparatus accordingto claim 52 or 56, where in the porous material comprises myocardial,peripheral muscle cells, or combinations thereof.
 60. The apparatusaccording to claim 52 or 56, comprising a porous intermediate materialfor contacting the damaged heart tissue, the porous intermediatematerial disposed below and in contact with the porous material.
 61. Theapparatus according to claim 52 or 56, comprising a cover for placementover the damaged cardiac tissue for sealing engagement with cardiactissue proximate the damaged cardiac tissue for maintainingsub-atmospheric pressure at the damaged cardiac tissue.
 62. Theapparatus according to claim 61, wherein the cover comprises a vacuumport disposed in gaseous communication with the vacuum source forreceiving sub-atmospheric pressure from the vacuum source.
 63. Theapparatus according to claim 61, wherein the cover comprises an adhesivesealing for adhering and sealing the cover to cardiac tissue surroundingthe damaged cardiac tissue.
 64. The apparatus according to claim 61,wherein the cover comprises a self-adhesive sheet.
 65. The apparatusaccording to claim 61, wherein the cover comprises a bio-incorporablematerial.
 66. The apparatus according to claim 65, wherein the covercomprises an electrospun material.
 67. The apparatus according to claim65, wherein the cover comprises a cast material.
 68. The apparatusaccording to claim 61, wherein the cover comprises an electrospunmaterial.
 69. The apparatus according to claim 61, wherein the covercomprises a cast material.
 70. The apparatus according to claim 61,wherein the cover comprises collagen.
 71. The apparatus according toclaim 68, wherein the cover comprises collagen.
 72. The apparatusaccording to claim 61, wherein the cover comprises a diol citrate. 73.The apparatus according to claim 68, wherein the cover comprises a diolcitrate.
 74. The apparatus according to claim 61, wherein the covercomprises poly 1,8-octanediol citrate.
 75. The apparatus according toclaim 68, wherein the cover comprises poly 1,8-octanediol citrate. 76.The apparatus according to claim 61, wherein the cover compriseschitosan.
 77. The apparatus according to claim 68, wherein the covercomprises chitosan.
 78. The apparatus according to claim 61, wherein thecover comprises polylactic acid.
 79. The apparatus according to claim68, wherein the cover comprises polylactic acid.
 80. The apparatusaccording to claim 52 or 56, wherein the vacuum source is configured tomaintain a sub-atmospheric pressure of about 50 mm Hg below atmosphericpressure at the damaged cardiac tissue.
 81. The apparatus according toclaim 52 or 56, wherein the vacuum source is configured to maintainsub-atmospheric pressure of between about 50 and 125 mm Hg belowatmospheric pressure at the damaged cardiac tissue.
 82. The apparatusaccording to claim 52 or 56, wherein the porous material comprises poressufficiently small to prevent the ingrowth of tissue therein.
 83. Theapparatus according to claim 82, wherein the porous material comprises apore size smaller than the size of fibroblasts.
 84. The apparatusaccording to claim 52 or 56, wherein the porous material comprisescollagen.
 85. The apparatus according to claim 52 or 56, wherein theporous material comprises chitosan.
 86. The apparatus according to claim52 or 56, wherein the porous material comprises polycaprolactone. 87.The apparatus according to claim 52 or 56, wherein the porous materialcomprises a polyglycolic and/or polylactic acid.
 88. The apparatusaccording to claim 52 or 56, wherein the porous material comprises aporous, open-cell collagen material.
 89. The apparatus according toclaim 52 or 56, wherein the porous material comprises a porous syntheticpolymer material.
 90. The apparatus according to claim 52 or 56, whereinthe porous material comprises at least one of a porous sheet and aflexible, sheet-like mesh.
 91. The apparatus according to claim 52 or56, wherein the porous material comprises two or more layers, with thelayer closest to the damaged cardiac tissue containing poressufficiently small at the interface between the porous material and thedamaged cardiac tissue to prevent the growth of tissue therein.
 92. Theapparatus according to claim 91, wherein the porous material comprises apore size sufficiently large to promote the formation of granulationtissue at a selected surface of the porous material.
 93. The apparatusaccording to claim 52 or 56, wherein the porous material comprises poressufficiently small at a surface of the porous material for placementproximate the damaged cardiac tissue to prevent the growth of tissuetherein.
 94. The apparatus according to claim 52 or 56, wherein theporous material comprises a pore size large enough to allow movement ofproteins the size of albumin therethrough to permit undesirablecompounds to be removed.
 95. The apparatus according to claim 52 or 56,wherein the porous material is sealed to prevent the transmission ofsub-atmospheric pressure through all surfaces but one.
 96. The apparatusaccording to claim 52 or 56, wherein the vacuum source comprises avacuum pump.
 97. A degradable or resorbable vacuum appliance fortreating injured or diseased tissues in a body, comprising a dressingconfigured to be implanted in the body, the dressing having a voidstructure configured to permit the transmission of sub-atmosphericpressure therethrough; and a bio-incorporable cover configured to beimplanted in the body to cover and enclose the dressing to provide achamber about the dressing in which sub-atmospheric pressure may bemaintained.
 98. The vacuum appliance according to claim 97, wherein thedressing comprises a bio-incorporable material.
 99. The vacuum applianceaccording to claim 98, wherein the rate of bio-incorporation of thedressing is higher at the periphery of the dressing than at the centerof the dressing.
 100. The vacuum appliance according to claim 97,wherein the dressing comprises an electrospun or cast material, orcombinations thereof.
 101. The vacuum appliance according to claim 97,wherein the dressing comprises synthetic molecules.
 102. The vacuumappliance according to claim 97, wherein the dressing comprisesnaturally occurring molecules.
 103. The vacuum appliance according toclaim 97, wherein the dressing comprises a combination of synthetic andnaturally occurring molecules.
 104. The vacuum appliance according toclaim 97, wherein the cover comprises an electrospun or cast material.105. The vacuum appliance according to claim 97, wherein the covercomprises synthetic molecules.
 106. The vacuum appliance according toclaim 97, wherein the cover comprises naturally occurring molecules.107. The vacuum appliance according to claim 97, wherein the covercomprises a combination of synthetic and naturally occurring molecules.108. The vacuum appliance according to claim 97, comprising anevacuation tube in gaseous communication with the dressing.
 109. Amethod for treating an organ, comprising enclosing the organ in anair-tight chamber, applying sub-atmospheric pressure to the organ, andmaintaining the sub-atmospheric pressure for a sufficient time toincrease the function of the organ.
 110. A method for treating an organ,comprising enclosing the organ in an air-tight chamber, applyingsub-atmospheric pressure to the organ, and maintaining thesub-atmospheric pressure for a sufficient time to increase the size ofthe organ.
 111. A method for treating an organ according to claim 110,wherein the chamber is larger than the organ and wherein thesub-atmospheric pressure is maintained until the organ has increased insize to fill the chamber.
 112. A method for treating an organ accordingto claim 109 or 110, wherein the sub-atmospheric pressure is appliedintermittently to the chamber.
 113. A method for treating an organaccording to claim 112, wherein the time in which the absolute value ofthe applied sub-atmospheric pressure is greater than diastolic bloodpressure is less than five minutes.
 114. A method for treating an organaccording to claim 112, wherein the time in which the absolute value ofthe applied sub-atmospheric pressure is less than the diastolic bloodpressure is less than ten minutes.
 115. An apparatus for treating anorgan, comprising an air-tight chamber configured to surround andcontain the organ, a vacuum source operably connected to the chamber forapplying and maintaining sub-atmospheric pressure to the organ.